SECTION 03: THE THYROID GLAND

By the end of Section 03, you should be able to:

• Describe the synthesis of thyroid hormone and outline the importance of iodine. •

• Describe the effects of thyroid hormones on metabolism and the consequences of hypo- and hyperthyroidism. •

• Understanding the control of thyroid hormone release, describe the various hormone levels during hypothyroidism and hyperthyroidism. •

• Describe the conditions that can lead to the formation of a goiter

📌 THYROID GLAND – QUICK NOTES

🔹 Location:

• Found just below the larynx (voice box)

• Sits on top of the trachea (windpipe)

THYROID GLAND 🔹 Structure:

• Has 2 lobes: Right lobe & Left lobe

• Lobes are connected by a thin bridge called the isthmus

• Looks like a butterfly in shape

THYROID GLAND 🔹 Function:

• Produces and releases thyroid hormones

  • These hormones help control metabolism, energy, and growth

• Both lobes work the same – no difference in function between them

THYROID GLAND 🔹 Inside the Gland:

• Has a special internal organization (not shown in the image)

• This structure helps it efficiently make and store hormones

THYROID GLAND – CELLULAR STRUCTURE 🔹 Follicular Cells

• Main secretory cells of the thyroid

• Form hollow spheres called thyroid follicles

• Responsible for making thyroid hormones (T3 & T4)

THYROID GLAND – CELLULAR STRUCTURE 🔹 Thyroid Follicles:

• Appear like rings under a microscope

• Each ring is made of follicular cells surrounding a center filled with colloid

📌 THYROID GLAND – CELLULAR STRUCTURE🔹 Colloid:

• Gel-like substance in the center of each follicle

• Made mostly of a protein called thyroglobulin

• Where thyroid hormones are made and stored

📌 THYROID GLAND – CELLULAR STRUCTURE🔹 C Cells (Parafollicular Cells):

• Found between the follicles

• Make the hormone calcitonin (helps lower blood calcium)

• Not involved in making thyroid hormones like T3/T4

📌 THYROID GLAND – CELLULAR STRUCTURE 🔹 Capillaries:

• Surround the follicles

• Carry hormones into the bloodstream

📌 THYROID GLAND – CELLULAR STRUCTURE 🔹 Capsule of Connective Tissue:

• Outer layer that protects and holds the thyroid together

📌 THYROID GLAND – CELLULAR STRUCTURE image

📌 THYROID HORMONES – QUICK NOTES 🔹 Made From:

• Both hormones are made from the amino acid tyrosine

• They both contain iodine (I)

🔹 T4 – Thyroxine (Tetraiodothyronine):

• Made of: 2 tyrosine + 4 iodine

• Makes up ~90% of thyroid hormones released

• Less active form

• Converted to T3 in target tissues for full effect

🔹 T3 – Triiodothyronine:

• Made of: 2 tyrosine + 3 iodine

• Makes up ~10% of thyroid hormones

• More active form

• Works faster and stronger than T4

🔹 Key Function (for both):

• T3 and T4

• Control metabolism, growth, development, and body temperature regulation

💡 Tip to Remember:

• The number in the name tells you the number of iodine atoms!

  • T4 = 4 iodines

  • T3 = 3 iodines

IMPORTANCE OF IODINE🔹 Where It Comes From:

• Iodine is taken in through the diet

• In blood, it circulates as iodide (I⁻)

• We need about 1 mg of iodine per week

IMPORTANCE OF IODINE 🔹 How the Thyroid Uses It:

• Follicular cells take tyrosine + iodide from the blood

• Used to make thyroid hormones (T3 and T4)

• The thyroid gland is very good at collecting iodide

📌 IMPORTANCE OF IODINE – QUICK NOTES 🔹 Storage:

• Thyroid stores extra hormone in the colloid (inside follicles)

• Hormones are held bound to thyroglobulin until needed

• This is unusual because most lipophilic hormones aren’t stored

🔹 Why Iodine Deficiency Is Rare in Canada:

• Table salt has iodine added (iodized salt)

• Most people get enough iodine from their food

🔹 Bonus Definition:

• Iodide (I⁻): The form of iodine found in the blood (oxidation state -1)

SYNTHESIS OF THYROID HORMONES – 🔹 Step 1: Thyroglobulin Production

• Inside the follicular cell, the ER + Golgi make thyroglobulin (Tg)

• Tg is sent into the colloid (middle of the follicle)

SYNTHESIS OF THYROID HORMONES 🔹 Step 2: Iodide Trapping

• Iodide (I⁻) from the blood is pulled into the cell using a Na⁺/I⁻ cotransporter

• Na⁺ moves down its gradient, helping I⁻ move against its gradient

SYNTHESIS OF THYROID HORMONES🔹 Step 3: Iodide Moves Into Colloid

• Iodide travels from inside the cell into the colloid space

SYNTHESIS OF THYROID HORMONES 🔹 Step 4: Iodide Organification

• The enzyme TPO (thyroperoxidase) turns iodide (I⁻) into reactive iodine (I⁰)

• Iodine attaches to tyrosine on the Tg molecule

  • 1 iodine = MIT (Monoiodotyrosine)

  • 2 iodines = DIT (Diiodotyrosine)

SYNTHESIS OF THYROID HORMONES 🔹 Step 5: Hormone Formation (Coupling Reaction)

• MIT + DIT → T3 (Triiodothyronine)

• DIT + DIT → T4 (Thyroxine)

• ❌ No MIT + MIT (This combo does not form hormones)

• T3 & T4 stay attached to Tg in the colloid until needed

SYNTHESIS OF THYROID HORMONES 🔹 Bonus: Hormone Release (Not numbered in slide but shown in image)

• When needed, Tg with T3 and T4 is taken back into the follicular cell

• Inside the cell:

  • Tg is broken down by lysosomes

  • Free T3 and T4 are released into the blood

RELEASE OF THYROID HORMONES 🔹 Step 1: Colloid is Taken In

• Follicular cells take in part of the colloid (which contains Tg + T3/T4)

• This happens through phagocytosis (cell “eating”)

• Forms vesicles inside the cell

RELEASE OF THYROID HORMONES 🔹 Step 2: Digestion by Lysosomes

• Lysosomes (cell “digesters”) fuse with the vesicle

• They use enzymes to break down thyroglobulin (Tg)

• This releases:

  • T3 (active)

  • T4 (less active)

  • MIT and DIT (recycled, not released)

RELEASE OF THYROID HORMONES 🔹 Step 3: T3 & T4 Enter Bloodstream

• T3 and T4 are lipophilic (fat-loving), so they easily cross the cell membrane

• Enter the bloodstream and bind to plasma proteins for transport

  • Main one: Thyroid-binding globulin

RELEASE OF THYROID HORMONES 💡 Reminder:

• Only T3 and T4 get released into blood

• MIT and DIT stay inside the cell and get reused

ACTIONS OF THYROID HORMONES 🔹 General Info:

• Acts on almost all body tissues

• Slow effects (can take hours)

• Long-lasting (effects stay even after hormone levels drop)

ACTIONS OF THYROID HORMONES 🔹 1. Metabolic Rate & Heat Production

• Increases basal metabolic rate (body's basic energy use)

• Raises oxygen use + energy use

• Makes body produce more heat (thermogenesis)

ACTIONS OF THYROID HORMONES 🔹 2. Intermediary Metabolism

• Affects how the body uses fuel (like glucose and protein)

• Low hormone levels:
  → promotes glycogen storage + protein building

• High hormone levels:
  → promotes glycogen breakdown + protein breakdown

ACTIONS OF THYROID HORMONES 🔹 3. Sympathomimetic Effect

• Makes cells more responsive to catecholamines (like adrenaline)

• How? → Increases number of receptors for catecholamines

📌 ACTIONS OF THYROID HORMONES 🔹 4. Cardiovascular Effects

• Increases heart rate + contraction strength → raises cardiac output

• Increases blood flow + blood volume

• ❌ No effect on blood pressure

ACTIONS OF THYROID HORMONES 🔹 5. Growth

• Helps release growth hormone (GH) + insulin-like growth factor (IGF)

• Supports new protein building + bone growth

• Essential for normal growth in children

Hypothalamic-Pituitary-Thyroid (HPT) Axis - What starts the process?

Trigger:

• Stress (or low thyroid hormone levels)

Effect:

• Stimulates the hypothalamus.

Hypothalamic-Pituitary-Thyroid (HPT) Axis - What does the hypothalamus do?

Secretes:

• TRH (Thyrotropin-Releasing Hormone)

Target:

• Anterior pituitary

Hypothalamic-Pituitary-Thyroid (HPT) Axis - What does the anterior pituitary do?

Secretes:

• TSH (Thyroid-Stimulating Hormone)

Target:

• Thyroid gland

Hypothalamic-Pituitary-Thyroid (HPT) Axis What does the thyroid gland do?

Releases:

• Thyroid hormones: T₃ and T₄

Hypothalamic-Pituitary-Thyroid (HPT) Axis What do T₃ and T₄ do in the body?

Effects:

• ↑ Metabolic rate and heat production

• ↑ Growth and CNS development

• ↑ Sympathetic activity (fight or flight)

Hypothalamic-Pituitary-Thyroid (HPT) Axis How is the system controlled?

Negative feedback:

• High T₃ and T₄ levels signal the hypothalamus and pituitary to stop releasing TRH and TSH

• Prevents too much thyroid hormone

Hypothalamic-Pituitary-Thyroid (HPT) Axis What happens if TSH is missing or too much?

• No TSH → Thyroid shrinks

• Too much TSH → Thyroid grows (enlarges follicles)

What is Hypothyroidism?

Definition:

• A condition where the thyroid gland doesn't make enough T₃ and T₄ (thyroid hormones).

Also called:

• Low thyroid or underactive thyroid

Symptoms of Hypothyroidism (general idea)

• Fatigue

• Weight gain

• Cold intolerance

• Slowed metabolism

Hypothyroidism Cause #1 — Primary Failure of the Thyroid Gland

What happens?

• Thyroid itself is damaged (e.g. Hashimoto’s thyroiditis, an autoimmune disease)

Hormone levels:

• ↓ T₃ and T₄

• ↑ TSH (because there’s no negative feedback!)

Hypothyroidism Cause #2 — Secondary Failure

What happens?

• The hypothalamus or pituitary doesn’t work properly → ↓ TRH or ↓ TSH → ↓ T₃ and T₄

Hormone levels:

• ↓ T₃ and T₄

• ↓ TRH and/or ↓ TSH (depends on where the problem is)

Hypothyroidism Cause #3 — Low Iodine in Diet

What happens?

• Iodine is needed to make T₃ and T₄, so not enough iodine = not enough thyroid hormone

Hormone levels:

• ↓ T₃ and T₄

• ↑ TSH (same as primary failure—no negative feedback)

Most common cause worldwide!

Definition Recap

🧪 Primary failure = Problem in the thyroid gland itself
🧠 Secondary failure = Problem in hypothalamus or pituitary (the control centers)

Symptoms of Hypothyroidism - Why do symptoms happen?

Thyroid hormones (T₃ & T₄) control:

• Metabolism

• Growth

• Nervous system function
  So when they’re low, everything slows down.

Common Symptoms of Hypothyroidism

🧊 Cold intolerance
⏳ Slower reflexes
💭 Reduced mental alertness
😴 Easily fatigued
❤ Slow, weak heart rate
⚖ Weight gain (due to ↓ basal metabolic rate)

What is Cretinism?

🍼 Congenital hypothyroidism = Born with low thyroid hormone
🧠🧍‍♀ Results in:

• Dwarfism (short stature)

• Intellectual disability
  💡 Because thyroid hormones are essential for growth and brain development

What is Hyperthyroidism?

Definition:

• A condition where the thyroid makes too much T₃ and T₄

• Everything in the body speeds up

Hyperthyroidism Cause #1 — Secondary Failure (Tumors in Hypothalamus or Pituitary)

What happens?

• A tumor in the hypothalamus (↑ TRH) or pituitary (↑ TSH) causes constant stimulation of the thyroid

Hormone levels:

• ↑ T₃ and T₄

• ↑ TRH and/or ↑ TSH

• ❌ No negative feedback control (tumor ignores it)

Hyperthyroidism Cause #2 — Thyroid Tumor

What happens?

• Tumor in the thyroid gland itself → overproduces T₃ and T₄

Hormone levels:

• ↑ T₃ and T₄

• ↓ TSH (because of negative feedback from high T₃ and T₄)

Hyperthyroidism Cause #3 — Graves’ Disease (Most Common Cause)

What happens?

• An autoimmune disease

• The body makes LATS (long-acting thyroid stimulator)

• LATS mimics TSH and overstimulates the thyroid

• But LATS ignores negative feedback

Hormone levels:

• ↑ T₃ and T₄

• ↓ TSH

• ❌ LATS is not regulated

Quick Recap — Hyperthyroidism Causes & Hormones

Hyperthyroidism Why do symptoms happen?

🌀 Too much T₃ and T₄ = Everything in the body speeds up
⚡ High metabolism, high energy use, overactive systems

Common Symptoms of Hyperthyroidism

❤ Increased heart rate
🔥 Excessive heat production (feel hot/sweaty)
💪 Muscle weakness (from protein breakdown)
😠 Mood swings (irritable, anxious from ↑ CNS activity)
⚖ Weight loss (even with more eating)
📈 Elevated basal metabolic rate

Hyperthyroidism Special Symptom — Graves’ Disease

👀 Exophthalmos = Bulging eyes

• Caused by fluid buildup from water-retaining carbs behind the eyes

• Most commonly seen in Graves’ disease

Hyperthyroidism vs Hypothyroidism (Quick Compare)

What is a Goiter?

🦠 Goiter = Enlarged thyroid gland
👀 Often visible in the neck
📈 Caused by too much TSH stimulation → increases size and number of thyroid follicles

When Does a Goiter Form?

A goiter forms any time TSH is high, even if thyroid hormones (T₃/T₄) are low or high.

Goiter in Hypothyroidism

🧪 Primary hypothyroidism (e.g. Hashimoto’s or iodine deficiency):

• ↓ T₃/T₄

• ↑ TSH (due to lack of negative feedback)
  ✅ Goiter present

Goiter in Hyperthyroidism

💉 Graves’ disease:

• LATS (autoantibody) acts like TSH and overstimulates the thyroid

• TSH is ↓, but LATS still causes thyroid growth
  ✅ Goiter present

🧠 Pituitary tumor (secondary hyperthyroidism):

• ↑ TSH from tumor → overstimulates thyroid
  ✅ Goiter present

When is Goiter Not Present?

• Thyroid tumor: ↑ T₃/T₄ but ↓ TSH (because of negative feedback)
  ❌ No goiter — TSH is low

• Secondary hypothyroidism: Low TSH & TRH due to pituitary/hypothalamus issue
  ❌ No goiter — no TSH to stimulate thyroid

Summary Table — Goiter or Not?

What causes a goiter?

A goiter forms when the thyroid is overstimulated by TSH (or anything acting like TSH like LATS)
⬆ TSH or LATS = Goiter
⬇ or 🚫 TSH = No Goiter

Goiter in Hypothyroidism – Primary Failure

🧠 What happens?

• Thyroid can't make T₃/T₄ → No negative feedback → TSH increases
  ✅ Goiter Present

Goiter in Hypothyroidism – Secondary Failure

🧠 What happens?

• Problem in pituitary or hypothalamus → ↓ TRH and/or ↓ TSH → ↓ T₃/T₄
  ❌ No Goiter (not enough TSH to stimulate growth)

Goiter in Hypothyroidism – Iodine Deficiency

🧠 What happens?

• No iodine = No T₃/T₄ → TSH rises due to lack of feedback
  ✅ Goiter Present

Goiter in Hyperthyroidism – Pituitary or Hypothalamic Tumor

🧠 What happens?

• Tumor makes too much TRH or TSH → ↑ T₃/T₄ AND ↑ TSH
  ✅ Goiter Present

Goiter in Hyperthyroidism – Thyroid Tumor

🧠 What happens?

• Tumor makes lots of T₃/T₄ → Negative feedback ↓ TSH
  ❌ No Goiter (low TSH = no stimulation)

Goiter in Graves’ Disease

🧠 What happens?

• LATS antibody mimics TSH → Constant stimulation of thyroid
  ✅ Goiter Present

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